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Association between genome-wide epigenetic and genetic alterations in breast cancer tissue and response to HER2-targeted therapies in HER2- positive breast cancer patients: new findings and a systematic review

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Cancer Drug Resistance 2022年第4期5卷 995-1015页

作者： Daniela Furrer Dzevka Dragic Sue-ling Chang Frédéric Fournier Arnaud Droit Simon Jacob caroline Diorio Centre de Recherche sur le cancer de l’Universitélaval 1050 Avenue de la MédecineQuébecQC G1V 0A6Canada Axe Oncologie Centre de Recherche du CHU de Québec-UniversitéLavalQuébecQC G1S 4L8Canada Département de médecine sociale et préventive Facultéde MédecineUniversitéLavalQuébecQC G1V 0A6Canada UniversitéParis-Saclay UVSQInsermCESP U1018Exposome and Heredity TeamGustave RoussyVillejuif 94807France Département de médecine moléculaire Facultéde MédecineUniversitéLavalQuébecQC G1V 0A6Canada Département de biologie moléculaire de biochimie médicale et de pathologieFacultéde MédecineUniversitéLavalQuébecQC G1V 0A6Canada Centre des Maladies du Sein Hôpital du Saint-SacrementQuébecQC G1S 4L8Canada

Recent evidence suggests that genetic and epigenetic mechanisms might be associated with acquired resistance to cancer therapies.The aim of this study was to assess the association of genome-wide genetic and epigenetic alterations with the response to anti-HER2 agents in HER2-positive breast cancer patients.PubMed was screened for articles published until March 2021 on observational studies investigating the association of genome-wide genetic and epigenetic alterations,measured in breast cancer tissues or blood,with the response to targeted treatment in HER2-positive breast cancer patients.Sixteen studies were included in the review along with ours,in which we compared the genome-wide DNA methylation pattern in breast tumor tissues of patients who acquired resistance to treatment (case group, n = 6) to that of patients who did not develop resistance (control group, n =6). Among genes identified as differentially methylated between the breast cancer tissue of cases and controls, oneof them, PRKACA, was also reported as differentially expressed in two studies included in the review. Althoughincluded studies were heterogeneous in terms of methodology and study population, our review suggests thatgenes of the PI3K pathway may play an important role in developing resistance to anti-HER2 agents in breastcancer patients. Genome-wide genetic and epigenetic alterations measured in breast cancer tissue or blood mightbe promising markers of resistance to anti-HER2 agents in HER2-positive breast cancer patients. Further studiesare needed to confirm these data.

关键词： Breast neoplasms epigenetics genetics HER2 inhibitors treatment response biomarkers

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Copper-uptake mediated by an ecofriendly zwitterionic ionic liquid: A new challenge for a cleaner bioeconomy

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Journal of Environmental Sciences 2023年第8期130卷 92-101页

作者： Marie E.Vuillemin Christophe Waterlot Anthony Verdin Sylvain laclef Christine Cézard David lesur Catherine Sarazin Dominique Courcot caroline Hadad Eric Husson Albert Nguyen Van Nhien Enzyme and Cell Engineering UMR 7025 CNRSUniversity of Picardie Jules Verne-Faculty of Sciences33 rue Saint Leu80039 Amiens CedexFrance University of lille Mines-Télécom InstituteUniversity of ArtoisJUNIAULR 4515-LGCgELaboratory of Civil Engineering and Geo-EnvironmentF-59000 LilleFrance Environmental Chemistry and life Interactions Unit UCEIV UR4492FR CNRS 3417University of Littoral Cote d’Opale(ULCO)DunkerqueFrance laboratory of Glycochemistry Antimicrobials and AgroresourcesUMR CNRS 7378University of Picardie Jules Verne-Faculty of Sciences33 rue Saint Leu80039 Amiens CedexFrance Institute of Chemistry of Picardie FR CNRS 3085 80039 AmiensFrance

This study aims to investigate the ability of an imidazolium biobased Zwitterionic Ionic liquids(ZIls)in enhancing the phytoavailability of copper from garden(G)and vineyard(V)soils using the model plant ryegrass.Uncontaminated and artificially contaminated CuSO_(4) soils,unamended and ZIl-amended soil modalities were designed.The copper/ZIl molar ratio(1/4)introduced was rationally established based on molecular modeling and on the maximal copper concentration in artificially contaminated soil.Higher accumulation of copper in the shoots was detected for the uncontaminated and copper contaminated ZIl amended V soils(18.9 and 23.3 mg/kg,respectively)contrary to G soils together with a ZIl concentration of around 3%(W/W)detected by lC-MS analyses.These data evidenced a Cu-accumulation improvement of 38%and 66%compared to non-amended V soils(13.6 and 13.9 mg/kg respectively).ZIl would be mainly present under Cu(II)-ZIl_(4) complexes in the shoots.The impact on the chemical composition of shoot was also studied.The results show that depending on the soils modalitity,the presence of free copper and/or ZIl led to different chemical compositions in lignin and monomeric sugar contents.In the biorefinery context,performances of enzymatic hydrolysis of shoots were also related to the presence of both ZIl and copper under free or complex forms.Ecotoxicity assessment of the vineyard soil samples indicated that the quantity of copper and ZIl remaining in the soils had no significant toxicity.ZIl amendment in a copper-contaminated soil was demonstrated as being a promising way to promote the valorization of phytoremediation plants.

关键词： Cu-accumulation Biobased Zwitterionic Ionic liquid (ZIl) Enzymatic hydrolysis Ecotoxicity

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Hepcidin levels in hereditary hyperferritinemia:Insights into the iron-sensing mechanism in hepatocytes

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World Journal of Gastroenterology 2010年第28期16卷 3541-3545页

作者： Jayantha Arnold Arvind Sangwaiya Vijay Manglam Mark Thursz caroline Beaumont caroline Kannengiesser Mark Busbridge Department of Gastroenterology Ealing HospitalLondonUB1 3HWUnited Kingdom Department of Hepatology St Mary's Hospital Imperial College LondonLondonW2 1NYUnited Kingdom Biochemical hormones and Genetics laboratory Bichat Claude Bernard Hospital46Rue Henri HuchardParis75018France Clinical Chemistry Hammersmith Hospital Imperial College LondonLondonW6 8RFUnited Kingdom

AIM:To study the role of hepcidin in hereditary hyperferritinemia cataract syndrome(HHCS). METHODS:Six patients from two families with HHCS, confirmed by genetic analysis showing A to G mutation at position+40 in the l-ferritin gene,were recruited to undergo serum hepcidin and prohepcidin measurements using radioimmunoassay and enzyme linked immunoassay,respectively,and measurements were compared with levels in serum from 25 healthy volunteers(14 females),mean age 36±11.9 years.RESUlTS:The serum hepcidin and prohepcidin levels in patients with HHCS were 19.1±18.6 and 187± 120.9 ng/ml,respectively.Serum ferritin was 1716.3± 376μg/l.liver biopsy in one patient did not show any evidence of iron overload.Serum hepcidin and prohepcidin values in healthy controls(HCs)were 15.30±15.71 and 236.88±83.68 ng/ml,respectively,while serum ferritin was 110±128.08μg/l.There was no statistical difference in serum hepcidin level between the two cohorts(19.1±18.6 ng/ml vs 15.30±15.71 ng/ml,P= 0.612)using two-tailed t-test. CONClUSION:Serum hepcidin levels in HHCS patients is similar to that in HCs.Our study suggests that circulating ferritin is not a factor influencing hepcidin synthesis and does not have a role in the iron-sensing mechanism in hepatocytes.

关键词： Hereditary hyperferritinemia Hereditary hyperferritinemia cataract syndrome Hepcidin Hepcidin assay Iron-sensing mechanism Iron responsive element Ferritin

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Influence of food availability,plant productivity,and indigenous forest use on ranging behavior of the endangered samango monkey(Cercopithecus albogularis schwarzi),in the Soutpansberg Mountains,South Africa

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Integrative Zoology 2020年第5期15卷 385-400页

作者： Edwin J.PARKER Russell A.HIl Andrew T.l.AllAN caroline HOWlETT Nicola F.KOYAMA School of Natural Sciences and Psychology Liverpool John Moores UniversityLiverpoolUK Primate and Predator Project Lajuma Research CentreLouis TrichardtSouth Africa Department of Anthropology Durham UniversityDurhamUK Department of Zoology University of VendaThohoyandouSouth Africa School of Anthropology and Conservation University of KentKentUK

Understanding the determinants of ranging patterns in species susceptible to habitat fragmentation is fundamental for assessing their long-term adaptability to an increasingly human-dominated landscape.The aim of this study was to determine and compare the influence of ground-based food availability,remotely sensed plant productivity,and indigenous forest use on the ranging patterns of the endangered samango monkey(Cercopithecus albogularis schwarzi).We collected monthly ranging data on two habituated samango monkey groups,from February 2012 to December 2016,from our field site in the Soutpansberg Mountains,South Africa.We used linear mixed models to explore how food availability,plant productivity,and indigenous forest use influenced monthly ranging patterns,while controlling for group size,number of sample days and day length.We found that as more areas of high plant productivity(derived from remotely sensed EVI)were incorporated into the ranging area,both total and core monthly ranging areas decreased.In addition,both total ranging area and mean monthly daily path length decreased as more indigenous forest was incorporated into the ranging area.However,we found no effect of either ground-based food availability or remotely sensed plant productivity on ranging patterns.Our findings demonstrate the behavioral flexibility in samango monkey ranging,as samangos can utilize matrix habitat during periods of low productivity but are ultimately dependent on access to indigenous forest patches.In addition,we highlight the potential of using remotely sensed areas of high plant productivity to predict ranging patterns in a small ranging,forest-dwelling guenon,over ground-based estimates of food availability.

关键词： food availability forest use plant productivity ranging patterns remote sensing samango monkey

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Human dNK cell function is differentially regulated by extrinsic cellular engagement and intrinsic activating receptors in first and second trimester pregnancy

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Cellular & Molecular Immunology 2017年第2期14卷 203-213页

作者： Jianhong Zhang caroline E Dunk Melissa Kwan Rebecca l Jones lynda K Harris Sarah Keating Stephen J lye Research Centre for Women's and Infants' Health Lunenfeld-Tanenbaum Research Institute Mount Sinai Hospital Toronto ON M5T 3H7 Canada Department of Obstetrics & Gynaecology University of Toronto Toronto ON M5G 1 L4 Canada Department of Physiology University of Toronto Toronto ON M5G 1L4 Canada Institute of Human Development University of Manchester Manchester M 13 9WL UK St. Mary's Hospital Central Manchester University Hospitals NHS Foundation Trust Manchester Academic Health Science Centre Manchester M13 9WL UK Department of Pathology University of Toronto Toronto ON M5G 1L4 Canada

Decidual natural killer （dNK） cells express an array of activation receptors to regulate placental immunity and development during early pregnancy. We investigated the functional character of human dNK cells during the first and second trimester of gestation and the interaction between dNK and trophoblast cells. Although the frequency of CD56＋CD16-dNK among the total CD45＋ leukocytes did not change over this period, the expression of the activating receptors, NKp80 and NKG2D, was greatly upregulated. We observed a significantly higher number of extravillous trophoblast cells in proximity to the dNK cells in the first trimester in comparison with the second trimester decidua. NKG2D expression by first trimester dNK cells was decreased when co-cultured with the HTR-8 trophoblast cell line. In the second trimester, functional markers of dNK activation, i.e., angiogenic factor production （e.g., vascular endothelial growth factor, interleukin-8, interferon-gamma）, remained stable despite an increase in NKp80 or NKG2D surface expression. Furthermore, the degranulation capacity of dNK cells, as assessed by CD107a, was decreased in the second trimester. We suggest that in the first trimester, trophoblast-dNK interactions generate a population of dNK cells with a suppressed activating phenotype. In the second trimester, the loss of trophoblast-dNK interactions led to the inhibition of dNK cell function, although their activating receptor expression was increased. We speculate that during pregnancy, two mechanisms operate to modulate the dNK cell activation：suppression of activating receptor levels in the first trimester by trophoblasts and disengagement of receptor-ligand coupling in the second trimester.

关键词： decidual NK cells IFN-gamma NKG2D NKp80 pregnancy

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Impact of on-range choice feeding with black soldier fly larvae(Hermetia illucens)on flock performance,egg quality,and range use of free-range laying hens

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Animal Nutrition 2018年第4期4卷 452-460页

作者： Isabelle Ruhnke Camille Normant Dana l.M.Campbell Zafar Iqbal caroline lee Geoff N.Hinch Julie Roberts Faculty of Science AgricultureBusiness and LawSchool of Environmental and Rural ScienceUniversity of New EnglandArmidaleNSW 2351Australia Institut Polytechnique laSalle Beauvais 60000 BeauvaisFrance F.D.McMaster laboratory Commonwealth Scientific and Industrial Research Organisation(CSIRO)ArmidaleNSW 2350Australia

Semi-intensive free-range farm systems are common in Australia, and these systems frequently practise on-range feeding. The objective of this study was to investigate the benefit of on-range choice feeding on flock performance, egg quality, and range use of free-range laying hens using black soldier fly larvae(Hermetia illucens, BSF). A total of 160 mature ISA brown laying hens, previously determined to range daily, were allocated to a control group(control) or a treatment group(BSF) with various replicates depending on the parameter investigated. All hens were fed ad libitum indoors with a wheat-soy based diet formulated according to breed requirements. Black soldier fly hens were offered dried BSF larvae ad libitum on the range. Body weight, feed intake, BSF intake, egg production, feed conversion ratio, internal and external egg quality parameters, and individual range use using radio-frequency identification(RFID)technology was evaluated. Black soldier fly hens consumed on average 15 ± 1.7 g BSF larvae/hen per day.There were no differences between BSF and control hens for any of the performance parameters obtained(P > 0.05). Egg weight, shell weight, and shell thickness of eggs from BSF hens were significantly lower(P = 0.003, P = 0.001, and P = 0.004, respectively) than those of eggs from control hens. Egg yolk colour was significantly paler in eggs from BSF hens(P l hens were observed(P > 0.05) except for BSF hens showing longer total maximum time for a single visit to the range(P = 0.011). In conclusion, the average intake of BSF larvae indicated a good level of acceptance. Feed formulation should be adjusted for the intake of the choice fed source. The impact of choice-feeding on range use was minor.

关键词： Behaviour Chicken Insect protein Nutrition Poultry Radio-frequency identification

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An international multicentric phaseⅢrandomized controlled trial of time-acupoints-space acupuncture for the prevention of chemotherapy-induced fatigue in patients with early stage breast cancer:a study protocol

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Journal of Traditional Chinese Medicine 2022年第2期42卷 289-295页

作者： Saghachian Mahasti Barry caroline Asselain Bernard lI Yunfen NIE Jianyun lIU Dequan CHEN Dedian CHEN Chunxin laura Estevez lI Wenhui Jean-Pierre Armand ZHU Miansheng JU liya Institute Gustave Roussy ParisFrance Research Center of Epidemiology and public health ParisFrance Institute Curie of Paris ParisFrance Yunnan Cancer Hospital Third Affiliated Hospital of Kunming Medical UniversityKunmingChina PreciMed Platform Europe ParisFrance MD Anderson Cancer Hospital MadridSpain ARIATAS Association pour la Recherche et l’Information de l’Acupuncture Time-Acupoints-Space ParisFrance Yunnan Zhu's expert workstation National famous traditional Chinese medicine expert of Mian-Sheng ZHUKunmingChina

OBJECTIVE:To determine the difference in prevention of chemotherapy-induced fatigue between time-acupointsspace acupuncture(ATAS)administered weekly compared to sham acupuncture and non-acupuncture in patients with early breast cancer receiving adjuvant chemotherapy by epirubicine-cyclophosphamide(EC)followed by paclitaxel,as measured by the multidimensional fatigue inventory(MFI)over the previous week and Visual Analogue Scale measuring fatigue(VAS-F),and to evaluate the effects of ATAS on selfreported neuropathy pain,sleep,anxiety and depression.METHODS:In this multicenter clinical trial,we have randomized patients into 3 groups:ATAS,Sham and nonacupuncture with an unequal randomization of 2∶1∶1.A cloud related electronical clinical report form and smartphone platform was established for data entry.Patients with a history of stageⅠ-Ⅲbreast cancer scheduled to receive adjuvant chemotherapy.Acupuncture will be delivered once a week during chemotherapy with VAS-F evaluation.In order to qualify and quantify the mechanism of fatigue induced by chemotherapy with or without acupuncture,an evaluation of immune profiling was incorporate in this study.RESUlTS:The presence and seriousness of chemotherapy-induced fatigue should be considered in therapeutic programs for early breast cancer treatment.Fatigue induced by adjuvant chemotherapy in patients with breast cancer remains a major concern affecting the quality of life significantly.Unfortunately,we do not have effective pharmacological interventions yet.And clinical trials of acupuncture in preventing chemotherapyinduced fatigue in patients with early breast cancer have not been reported.CONClUSION:The findings of the trial will allow us to determine the effects of acupuncture treatment approach.We will also be able to confirm whether ATAS is better than sham acupuncture and non-acupuncture treatments.

关键词： breast neoplasms chemotherapy adjuvant fatigue immunity clinical protocols time-acupoints-space acupuncture

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Detection of liver micrometastases from colorectal origin by perfusion CT in a rat model

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Hepatobiliary & Pancreatic Diseases International 2014年第3期13卷 301-308页

作者： caroline Hatwell Magaly Zappa Mathilde Wagner Nicolas Michoux Valérie Paradis Valérie Vilgrain léon Maggiori Yves Panis Department of Colorectal Surgery Beaujon Hospital (AP-HP) 100 boulevard du Général Leclerc 92118 Clichy France Research Unit Bichat-Beaujon INSERM U773 Université Paris VII (Denis Diderot) Paris France Department of Radiology Beaujon Hospital (AP-HP) 100 boulevard du Général Leclerc 92118 Clichy France Department of Pathology Beaujon Hospital (AP-HP) 100 boulevard du Général Leclerc 92118 Clichy France

BACKGROUND: Some patients with colorectal carcinoma have liver metastases(lMs) which cannot be detected by conventional imaging. This study aimed to assess whether hepatic perfusion changes induced by micrometastases can be detected by perfusion computed tomography(CT).METHODS: lMs were produced in rats by injecting carcinoma cells into the portal vein. Perfusion CT was performed at microscopic(day 10), interval(day 17), and macroscopic stage(day 34). Perfusion parameters were computed using a dualinput one-compartmental model.RESUlTS: Micro and macro lMs presented a mean diameter of 0.5 and 2.6 mm, respectively. Compared to controls, lMs at interval(1.1 mm) and macroscopic stage induced significant perfusion changes: a decrease of 42%(P=0.004) and 41%(P=0.029) in hepatic transit time and an increase of 292%(P=0.073) and 240%(P=0.001) in portal delay, respectively.CONClUSIONS: lMs with a mean diameter between 1.1 and2.6 mm induced significant hepatic perfusion changes, detected by CT. Such detection may help to select patients and propose chemotherapy at the time of primary tumor resection.

关键词： liver circulation colorectal liver micrometastasis perfusion imaging computed tomography

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A TDG/CBP/RARα Ternary Complex Mediates the Retinoic Acid-dependent Expression of DNA Methylation-sensitive Genes

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Genomics, Proteomics & Bioinformatics 2014年第1期12卷 8-18页

作者： Hélène léger caroline Smet-Nocca Amel Attmane-Elakeb Sara Morley-Fletcher Arndt G.Benecke Sebastian Eilebrecht Vaccine Research Institute INSERM U955Institut Mondor de Recherche Biomédicale Institut des Hautes tudes Scientifiques Unité de Glycobiologie Structurale et Fonctionnelle–CNRS UMR 8576 Group of NMR and Structural BiologyUniversité Lille 1 Unité de Glycobiologie Structurale et Fonctionnelle–CNRS UMR 8576 Neuroplasticity TeamUniversité Lille 1 CNRS UMR 7224 Université Pierre et Marie Curie

The thymine DNA glycosylase （TDG） is a multifunctional enzyme,which is essential for embryonic development.It mediates the base excision repair （BER） of G：T and G：U DNA mismatches arising from the deamination of 5-methyl cytosine （5-MeC） and cytosine,respectively.Recent studies have pointed at a role of TDG during the active demethylation of 5-MeC within CpG islands.TDG interacts with the histone acetylase CREB-binding protein （CBP） to activate CBP-dependent transcription.In addition,TDG also interacts with the retinoic acid receptor α （RARα）,resulting in the activation of RARα target genes.Here we provide evidence for the existence of a functional ternary complex containing TDG,CBP and activated RARα.Using global transcriptome profiling,we uncover a coupling of de novo methylation-sensitive and RA-dependent transcription,which coincides with a significant subset of CBP target genes.The introduction of a point mutation in TDG,which neither affects overall protein structure nor BER activity,leads to a significant loss in ternary complex stability,resulting in the deregulation of RA targets involved in cellular networks associated with DNA replication,recombination and repair.We thus demonstrate for the first time a direct coupling of TDG＇s epigenomic and transcription regulatory function through ternary complexes with CBP and RARα.

关键词： CREB-binding protein Thymine DNA glycosylase Retinoic acid receptor α Transcription regulation Cytosine DNA methylation Epigenomics

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Predictors for perioperative blood transfusion in elderly patients with extra capsular hip fractures treated with cephalo-medullary nailing

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Chinese Journal of Traumatology 2018年第1期21卷 16-19页

作者： M, All Fazal caroline Bagley Parag Garg Royal Free NHS Foundation Trust The Ridgeway Enfield EN2 8JL United Kingdom

我们的学习的 PurposeThe 目的是在老病人为 perioperative 输血决定预兆的因素和要求，额外的胶囊的新潮的破裂与 cephalo 髓的 device.MethodsSeventy 对待 -- 有与 cephalo 髓的钉对待的额外的胶囊的新潮的破裂的九个病人在学习被包... 详细信息

我们的学习的 PurposeThe 目的是在老病人为 perioperative 输血决定预兆的因素和要求，额外的胶囊的新潮的破裂与 cephalo 髓的 device.MethodsSeventy 对待 -- 有与 cephalo 髓的钉对待的额外的胶囊的新潮的破裂的九个病人在学习被包括。年龄，性别， ASA 等级，外科，外科手术前、手术后的血色素，一些医院停留，骨折类型，输的单位的数字和 30 天的死亡预定 recorded.ResultsThe 平均数年龄是 82.3 年。47 个病人经历了一根短钉子和 32 个病人一根长钉子；53.4% 病人手术后地要求了输血。输送在71.8%长钉子被要求( p ?l 和 20 个病人 3 分级( p ?? 0.05 ) 。一些在非输送组的医院停留是 13 天，在输送，组是 19 天(p ?? 0.05 ) 。在需要输血的病人的三十天的死亡是5%，在非输送，组是3.7%( p ?>? 0.05 ) .ConclusionPatient 年龄， ASA 等级，钉子的外科手术前的血色素和长度是为在在与cephalo髓的钉对待的老病人的额外的胶囊的新潮的破裂的 perioperative 输血的可靠预言者并且增强一条选择输送政策。

关键词：输血破裂胶囊预言外科手术 ASA 血色素输送

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